Identifying miRNA key players shaping epidermolysis bullosa

Epidermolysis Bullosa (EB) belongs to a group of rare genetic skin conditions, which cause the skin to blister and tear even upon a slight touch. The fragility of butterfly wings inspired the name butterfly children for patients suffering from this painful and devastating disease. The source of this condition lies in a changed blueprint (genes) of structurally important proteins, which function is to anchor the various skin layers. A defect or absence of such a structural protein will result in heavy blister formation in skin and inner linings after even mild mechanical trauma, accompanied by sore wounds with frequent inflammation and severe side effects. Depending on the affected protein, EB can be subcategorized in several groups. We will focus within this research project on the recessive dystrophic EB subform, which is characterized by a defect in the structural protein collagen VII. Missing collagen VII leads to severe blister formation and is tragically connected to a severe life-limiting frequent manifestation of a very aggressive form of squameous cell carcinoma (SCC). There is an ongoing controversial debate about the ultimate cause of developing SCC, discussing permenant skin-renewal in wound healding processes, inflammation factors and modified scaffolding as impact factors. One, so far neglected aspect is the influence of tiny molecules, so-called microRNAs, on the verge of cancer development in RDEB. The production of proteins, which establish the molecular machinery and structural components of our cells, relies on transcripts (messengerRNA) of the corresponding blueprint gene. The more copies of messengerRNA the more protein is produced by our cells. MicroRNAs are instrumental in regulating this production process by influencing the amount of messengerRNA existing at a certain timepoint within a cell. As demonstrated by many research groups, microRNAs are capable of modifying cellular activities inducing the development or progression of major diseases, including several forms of cancer. Hence, we have committed to investigate differences in skin cell microRNA patterns between RDEB patient versus non-RDEB SCC patient and healthy control group in our epigenetics & small molecules group within the EB House Austria. For the first time, our research project should bring disease relevant molecular mechanisms into light, which are suspected to be under the force of de-regulated microRNAs. Our results will establish the basis in our strive for developing new therapeutic strategies in fighting this devastating disease and its serious consequences.

No additional funding sources recorded.